In sphingolipid biosynthesis of fungi, inositolphosphorylceramide(IPC) synthase is responsible for transferring inositol phosphate from phosphatidylinositol to the fungal ceramide to form inositolphosphorylceramide. The presence of inositolphosphorylceramides have been demonstrated in yeast (S. cerevisiae) and in pathogenic fungi (C. albicans, Aspergillus fumigatus, H. capsulatum). Lester & Dickson, 26 Adv. Adv. Lipid Res. 253 (1993). It is also known that in the model yeast, S. cerevisiae, inositolphosphosphingolipids are essential for viability. Wells et al., 178 J. Bacteriol. 6223 (1996).
Moreover, although elements of the synthetic pathway for sphingolipids in fungi are shared by mammalian sphingolipid synthesis, the pathway is divergent at the step after formation of ceramide. Martin & Pagano, 159 Anal. Biochem. 101 (1986). Thus, inhibitors of IPC synthase are likely candidates for antifungal chemotherapy.
In a copending application, Ser. No. 08/882,767, Dickson, Lester and Nagiec characterized the IPC synthase gene (IPC1). In that application, the DNA sequence of IPC1 is disclosed, as is the corresponding amino acid sequence of the enzyme.